Age-related impairments in memory and in cholinergic signaling due to reduced blood glucose responses to epinephrine

Memory impairments accompany aging and can range in severity from mild deficits during healthy aging to debilitating conditions such as Alzheimer’s disease. The causes of these impairments are generally viewed in terms of anatomical, chemical, and physiological changes within the brain. However, age-related changes in peripheral neuroendocrine systems can alter central neurobiological processes and may underlie some types of memory deficits. Previous work in rodents and humans indicates that increases in blood glucose in response to endogenous epinephrine release are important for regulating memory formation and durability. In old rats, glucose is less responsive to epinephrine and becomes severely depleted in the extracellular fluid of the hippocampus during a cognitively demanding task, contributing to poor memory. Glucose supplementation restores extracellular fluid levels of glucose and reverses the associated memory impairments. The present work examines potential mechanisms by which reduced blood glucose responses to epinephrine may produce age-related memory impairments, with particular emphasis on the ability of exogenously administered epinephrine or glucose to attenuate deficits in memory processes. Several findings suggest fluctuations in glucose levels in the extracellular fluid may modulate memory processes by altering the release of the neurotransmitter acetylcholine, which may affect downstream processes important for the formation of durable memories. In particular, nicotinic acetylcholine receptor signaling mediates the calcium-dependent activation of the ERK/MAPK and CREB signaling cascades, which are widely implicated in activity-dependent neuronal plasticity. Age-related deficits in brain glucose availability may limit these cholinergic signaling processes and produce memory impairments. This is the major hypothesis guiding these studies.

Name thesis:degree_name

Ph.D.

Level thesis:degree_level

Dissertation

Discipline thesis:degree_discipline

Neuroscience

Grantor

University of Illinois at Urbana-Champaign

Year dc:date

2013

Author dc:creator

• Morris, Kenneth

Contributors dc:contributor

• Gold, Paul E.
• Korol, Donna L.
• Beverly, Joseph L.
• Chung, Hee Jung
• Galvez, Roberto

• Memory
• Aging
• Glucose
• Epinephrine
• Acetylcholine
• Hippocampus
• cAMP response element binding protein (CREB)

Statement dc:rights

• Copyright 2012 Kenneth Allen Morris

Language dc:language

en

Handle dc:identifier

http://hdl.handle.net/2142/42331

OAI identifier oai:identifier

oai:www.ideals.illinois.edu:2142/42331